Intraocular Pressure And Corneal Thickness Measurement Biology Essay

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Systemic medication is a drugs which in intake orally or injection, which have some reaction with different receptors of our body to product the expected results. For example, to kill painful, decrease the secretion and kill virus in our body etc. In this dissertation, we are concentrating on the relationship between the medication and the intraocular pressure (IOP), and how is the medication affect to the intraocular pressure. So we are focusing on cardiovascular medication, it is because cardiovascular pressure has a very close relationship with the IOP (Leske, 1983) and it shown in some of the studies if someone have a high blood pressure or the blood pressure problems who will have higher prevalence to get intraocular pressure problem. And it is because the systemic medication which would affect the blood pressure, either increase or decrease it.

The intraocular pressure measurement which is an important part of the routine eye test in UK, most of the patients who are aged over about 40 or the patient who has closed family glaucoma history, the IOP measurement should be involved in the routine eye test. The IOP measurement which is very important due to the result is one of the biggest risk to diagnose the patient have glaucoma potentially or not, although the result is not the only data which is considered by the practitioner. And the diagnosis also consider with the family history, age, race, cup and disc change, visual field defect etc. So if the patient who has high intraocular pressure, he/she may not be involve the glaucoma. But the patient should have a high prevalence to get a high blood pressure (Leske, 1983).

The first tonometry measurement technique which used by GP is digital palpation, and it is used the finger to estimate the pressure or the hardness between two closed eyes. The first one tonometer in the world is "Schiotz Tonometer" which introduced by Hjalmar August Schiotz in 1905 (Loffler). And this tonometer is using on the patient who are lying. It is because the rigidity of the eye may affect the result of the IOP measurement, Friedenwald introduced a revised table, called Friedenwald's nomogram, which to minimize the problem which affect the measurement. After the first tonometer introduce and used clinically, there are many other tonometer with different theory to be presented. The one of the marketed tonometer being a gold standard and used since it introduced in 1954 until now which is Goldmann tonometer and which is along the same idea and theory, Perkins tonometer introduced in 1965 (Loffler, 2006). They are based on the Imbert-Fick law which stated by three reasons: (1) it is accurate applied on the fine thin membrane; (2) it is accurate on applied on the elastic sphere surface; (3) it is accurate on applied on homogeneous elastic sphere (Jun, 2005).

With the reason of the IOP measurement is a important part of the routine eye test, and it will affect by the blood pressure, so there is why this dissertation started for the research of the "What impact do systemic medications have on intraocular pressure"

Keywords: Cardiovascular medication; intraocular pressure (IOP); tonometry;

Chapter 1 - Introducation

The topic of the dissertation is "What impact do systemic medications have on intraocular pressure"

"Systemic" stated affecting the whole body, not just the especially part of the body. (Mikel, 2005)

"Medication" stated that treating the disease or sickness of the body by drugs or some chemical substances. (Mikel, 2005)

"Intraocular pressure (IOP)" stated that it is pressure which is used to maintain the formation of the eyeball and also the value of the pressure is occurring by the amount of the drainage of the aqueous humour. (Millodot, 2004)

Nowadays, the people who living in developed countries or developing countries paid more attention of health of the eyes, it is the why some of the developed countries which will provide regular eye test to their nation, for example, U.K. Checking the eye pressure is one of the important part within the eye examination in UK, it is because the abnormal pressure of the eye is one of important factor of risk of glaucoma. And glaucoma is one of the popular eye diseases in the world. So the optometrist is very concern on the intraocular pressure (IOP).

Glaucoma may damage the visual function by mechanical theory and vascular ischaemic theory. Mechanical theory stated that the increase of the intraocular pressure which elongate the laminar beams and cause the damage ganglion cells on the retina (Josef, 2002). And the other theory, vascular ischaemic theory stated that the insufficient supply of the blood for the ganglion cell on the retina which cause by the increase of the intraocular or the other risk factors consequently (Josef, 2002).

Nowadays, there are many types of the diseases are discovered. And there are many drugs using to treat the illness in the world. Some of it may used for short term, e.g. the medication used to treat the flu or cold. And some of these medication will use for long term, it may used to control the abnormality or irregularity in our body, e.g. control the blood pressure or the level of the cholesterol etc. Most of these drugs are systemic drugs which are used by oral or injection, some of the study showed that there are some effects on the intraocular pressure (Leopold, 2001) (Volkan, 2005). And it is the main point why this dissertation started and it is because there is not many studies review the impact of intraocular pressure by the systemic medication.

In this dissertation, I will generally review different types of the systemic medication which may cause the effect on the IOP. It is because the blood pressure has very closed relationship with the intraocular pressure. Some of the systemic medications are reviewed that are mainly used to treat the cardiovascular disease and some other abnormality of the body. The main finding of this dissertation is going to find how much does the medication impact on the intraocular pressure (IOP). Some of the studies which going to review is measuring how are the ocular blood flow and some about the aqueous dynamic affect by the systemic medication.

I am looking the medication which may affect the IOP, the list is shown below:

Acetazolamide

Dexamethasone

Esmolol

Hormone replacement therapy (HRT)

Nitric Oxide

Sildenafil Citrate

Triamcinolone

Chapter 2 - Drugs

2.1 Acetazolamide

It is a carbonic anhydrase inhibitor which is used to decreases production of aqueous humor in the eye and the intraocular pressure. And it can decrease the excretion of renal tubule cells. It is because it can raise the water excretion by the kidney, so it may use a diuretic agent for the patient (Amy, 1996). It can be use as acute mountain sickness treatment agent as need while at high altitude (Amy, 1996)

2.2 Dexamethasone

It is a corticosteroid. As we know corticosteroid is used to treat the inflammatory condition. It can be formed as tablet, injection solution, eye drops and eye ointment for prescription (Hawthorn, 2003). For this medicine, it can be used to treat the rheumatic disease and shock & cerebral oedema by intravenous injection (Hawthorn, 2003). It also can used as diagnosis drug for Cushing disease why caused by exogenous glucocorticoids therapy commonly (Burch, 1994).

2.3 Esmolol

It is a beta-blocker which is used for cardio problem. They are controlling the muscle of the heart which block stimulates the beta receptors of the sympathetic nervous system by norepinephrine. The beta-blocker is commonly used to treat the hypertension in younger and older patients nowadays (Che, 2009). This can be used by orally or intravenous infusion. It is used to treat the heart arrhythmias which is the condition that the patient with irregular heartbeat rhythm (Mikel, 2005). Also it can be used to treat the hypertension that occurs after the surgery.

2.4 Hormone replacement therapy (HRT)

It is a continuous combined therapy with oestrogen and progestogen (both are the hormones) which are taken every day. It can be taken by tablet orally or taken by skin patch or implant. It is aim to produce a similar level of hormones which should be before the menopause (Westcott, 1993). Although there are many methods to do this therapy, and the common method which used by general practitioner is pill form. It is very common using in UK, US and Australia (Westcott, 1993). It is because it is easy to take and easy to adjust the dose of the therapy. This therapy is used to treat the vaginal dryness, cystitis-like symptoms and also it may helping some physical symptoms, for example, increasing energy and self-confidence during the menopause period.

2.5 Sildenafil Citrate

It also named a Viagra. This drug is going to inhibit the enzyme that metabolizes guanosine monophosphate (Nazzareno, 2005). It can be relax and inhibit the growth of the smooth muscle cell, including of lung. It can used to treat erectile dysfunction, which can improve the penile erection due to dilate the blood vessels in the corpus cavernosum (Boolell, 1996). And Sildenafil is developed to treat cardiac ischemic conditions (Jackson, 1999).

2.6 Triamcinolone

It is a systemic corticosteroid. This drug injection is used to treat the neovascular, inflammatory and some retinal disorders (Jonas, 2005), e.g. manage the hypercalcemia associated with cancer systemically (Amy). After the injection, the drugs compound will bind to the cytoplasmic receptors and produce the reaction to do the anti-inflammatory and immunosuppressive effects.

Chapter 3 - Intraocular Pressure & Measurement

3.1 Intraocular Pressure (IOP)

Intraocular Pressure (IOP) may affect by the corneal rigidity or the corneal thickness. Some report stated that the thicker the cornea, the higher the intraocular pressure and the thinner the cornea, the lower the IOP measurement result (Herndon, 1997). The clinical investigation of the routine eye test the normal IOP measurement value should be under 21mmHg. The mean IOP should be about 16mmHg (Asrani, 2000). Also the IOP should have a fluctuation due to the time of the day, e.g. morning and evening, heartbeat, level of blood pressure, respiration and medication. And the normal diurnal fluctuation is 4mmHg and the glaucoma eye may be 10mmHg or above (Loffler, 2006). The value of IOP is controlled by the rate of aqueous humor production by ciliary body and the drainage system of aqueous humor in the anterior eye through the canal of Schlemm (Duo, 2002). Also some of the fluid may pass from posterior chamber to anterior chamber through the pupil, but it is majority passing through by the trabecular network.

There are some factors may affect the IOP (Loffler, 2006):

The level of aqueous humor production

The obstruction encountered in the drainage system

The episcleral venous pressure

Other main vessel pressure of the eyes and non-pathological factors, such as age or the amount of of water or coffee intake.

3.2 Measurement of IOP

The measurement of intraocular pressure is called "Tonometry". It is measuring the pressure or tension of the eye. The instrument which is used to measure is called "Tonometer". Nowadays, tonometry is one of the important procedure to evaluate the patient have glaucoma or not in the normal eye test. There are different types of the tonometry, mainly divided into contact and non-contact. The theory of the former requires local anesthetic and the latter is not due to use the air puff and the sensor.

3.2.1 Contact tonometry

The first principle of contact tonometry is indentation theory. The instrument which developed by this theory is measuring the degree of impression or indentation produced by the known weight. The patient is required to lie horizontally and the instrument is placed on their cornea. But there is some problem of this theory of the measurement, such as surface tension force due the amount of thickness of tear film and the elasticity of ocular wall due to the thickness of cornea (Henson, 1996). The original design of this type of tonometer is a known weight of plunger rod which passed through a concave footplate, and the end of rod has the same curvature with the footplate which contacts to the eye.

Tonography is an electronic tonometer developed by the indentation theory. This instrument is required to left on the eye surface for several minutes. It is also assume that the IOP will rise initially and fall down gradually.

The second theory of tonometry is called "applanation tonometry". It stated that is measuring the force which can flatten a standard area of the corneal surface due to the Imbert-Fick law. The law stated that is accurate only for the spherical surface with thin membrane, perfectly dry, flexible and elastic. The value is measured by the external force which the fixed area is flattened.

Figure 1 Schiotz Tonometer

The first tonometer which is developed by this theory is Schiotz Tonometer which is using with the Friedenwald's nomogram (Elliott, 1997).

Figure 2 Goldmann Tonometer

The second tonometer which is developed by the applanation theory is Goldmann Tonometer. It is also a gold standard instrument of IOP measurement due to the accuracy. It is still a good guideline, standard and desirable instrument using by the eye care professional. And there are few reasons why the Goldmann tonometer is accuracy.

Due to dry surface of the Imbert-Fick law, the area of instrument head which contact to the corneal surface is about 3.06mm in diameter, covert to the amount of area is 7.35mm2. so the amount of fluid in applanated area is very small, so it can suit to the dry surface requirement (Moseley, 1983).

Due to the very small applanated area, it can be assume that the force which produces by the tear film is equal to force which applanate on the corneal surface

It is simple conversion due to the force in gram is equal to 1/10th of the IOP in mmHg (Henson, 1996).

The Goldmann tonometer is including applanated head and spring loaded lever. It is used mounting on a slit-lamp. When using Goldmann tonometer, the local anesthesia and fluorescein is required. During the examination, the applanated head is contacting to the corneal surface, and the practitioner would view the applanated area through the slit lamp microscope. The value of pressure is measured by adjusting the spring- loaded lever until the standard circular fluorescein pattern shown in the microscope. There are many advantages why the Goldmann tonometer being a standard in the professional field, (1) reasonable price; (2) eliminated corneal rigidity effect; (3) patients are not required to be lie (4) it is very important requirement either in practice or research - repeatable result.

After the Goldmann tonometer developed, the other according to applanation theory tonometer is "Perkin tonometer" which is usually seen and use in the practice.

3.2.2 Non-contact Tonometry (NCT)

There are few common non-contact tonometers, such as Reicher Non-Contact Tonometer, Keeler PulsAir Tonometer and Topcon CT-60 or CT-80. Both of them is used a same technique which is used a rapid air pulse to applanate the cornea and detected by the electro-optical system. The detected force of the air puff of the applanation which is the intraocular pressure measured (Schlote, 2005). The differenve between the non-contact tonometer and the Goldmann tonometer is about 3mmHg (Moseley, 1983). So the non-contact tonometer cannot be the standard to diagnosis, it play the role in the routine eye check as a fast and simple screening. But now, the result of modern non-contact tonometers is shown that the result is very correlated with Goldmann standard, such as a new non-contact tonometer, Reichert AT550 (Jorge, 2002). It is because the non-contact tonometry is measuring without any contact between the cornea and the instrument, so it can decrease the chance of disease transmission potentially. Therefore, if the performance of the non-contact tonometer is similar to the contact tonometry, the non-contact tonometer should be one of the standard for diagnosis and used more frequently in the practice.

Chapter 4 - Aqueous Humor and Anatomy of Eye

4.1 The aqueous humor system

The aqueous humor which is the fluid found in the eye in the anterior and posterior chamber. And it is clear and colourless liquid. It plays a very important role in the eye metabolism because the fluid brings the nutrients and oxygen for the avascular tissues in the eye, such as, cornea and the intraocular lens. There is some change of the opinion on the production of aqueous humor. The first theory of production is that the aqueous humor is produced by ciliary processes (Saude,). Then it changes the concept that the fluid is produced by ultrafiltration and dialysis. Nowadays, the modern and general theory showed that the aqueous humor is produced or secreted by the cililary epithelium. For the components of aqueous humor, it contains electrolytes, glucose, ascorbic acid, protein etc. and also sodium and chloride (Saude).

There is an outflow system with different level to help the aqueous humor circulation. The obvious one is trabecular meshwork, and then to the Schlemm's canal which located in the sclera tissues. After that, it will drain into the anterior ciliary veins. The other system is is uveoscleral drainage system, it is working when the pressure in suprachoroid is 2-4mmHg lower than the pressure in the anterior chamber (Forrester, 2002), some of the glaucoma treatment is using this drainage system by rising the outflow of this system to decrease the intraocular pressure (Forrester, 2002), such as prostaglandin. The last system is episcleral circulation, which is working the intraocular pressure is over 15 mmHg as shown many years ago study (Forrester, 2002). The aqueous will drain into the the Schlemm's canal by trabecular meshwork and then into the episcleral vein.

Function of aqueous humor

Bring the oxygen and nutritions to the avascular ocular tissue, e.g. cornea

Being a metabolism agent for for the avascular tissues

Retain the intraocular pressure and keep the shape of the eyeball

Defend the pathogens due to the immunogloblulins in the aqueous by immune reaction

4.2 Episcleral Vein

The episcleral vein located in the outer layer of sclera which is called "episclera", and it is position near the edge of the cornea and the system of trabecular meshwork. The episcleral vein got a very close relationship with the outflow of the aqueous humor, and aqueous humor outflow system is correlated with the intraocular pressure. And episcleral vein is one of the drainage systems of the aqueous humor. Some of the study showed that there is a pressure change of the episcleral vein. Some of the study show that when the episcleral vein pressure changes, the intraocular pressure will change also. And the value show that they are very similar, if the episcleral vein change about 1mmHg, the IOP will also change 1mmHg (Friberg, 1987).

And the blood pressure is correlated with the ocular pressure if there is the change of the blood pressure and showed in some previous study (Bulpitt, 1975). So it means that episcleral vein pressure, blood pressure and intraocular pressure has very closed relationship between them. And some of the system treatments or therapies show that there are some changes with those pressures of three of them. It is also the main point why this dissertation is created

Chapter 5 - Finding

Acetazolamide

Range(mmHg)

Duration of treatment

Control Group

Pre-treatment

Intraocular pressure

10.0 - 21.0

Post-treatment

Intraocular pressure

6hrs after treatment

14.0 - 31.5

Post-treatment

Intraocular pressure

24 hours after treatment

12.0 - 27.0

Table 1. The intraocular pressure of the range between the pre-treatment and the post-treatment of the drug acetazolamide

The difference between the pre-treatment and post-treatment is increasing from 12.0 - 21.0 to 14.0 - 31.5 in the duration of treatment is about 6 hours after the first treatment has been taken in the control group. The range between before the treatment and after the treatment is about 10mmHg in 6 hours after the treatment. The percentage of the range is different with the pre-treatment is about 45% increase. The different between the pre-treatment and post-treatment in the control group is increasing about 5mmHg after 24 hours treatment. The percentage of the range between it change is about 28% increase.

For the treatment group which is taking acetazolamide. The difference between the pre-treatment and post-treatment is increasing about 4.5mmHg after 6hours treatment. The percentage of this group change is about 21.4% increase. And after 24 hours treatment, the intraocular pressure is significant decrease about 3mmHg. The decrease percentage is about 25% in the treatment group which took 24 hours treatment.

Acetazolamide

Mean ± SD (mmHg) (95% confidence intervals)

Duration of treatment

Control Group

Pre-treatment

Intraocular pressure

15.69 ±2.76

Post-treatment

Intraocular pressure

6hrs after treatment

20.1 ±5.57

Post-treatment

Intraocular pressure

24hours after treatment

16.15 ±2.99

Table 2. The chart of mean and standard deviation between intraocular pressure of the the pre-treatment and the post-treatment of the drug acetazolamide in 6 hours and over 1 week treatment

Table 2 shows the mean change of the intraocular pressure. For the control group, the value of the treatment which taken after 6 hours, the mean of IOP will going higher than before treatment about 4mmHg, and the standard deviation is also increase from 2.76 to 5.57. After one week treatment, the difference between the pre-treatment and post-treatment, the mean of IOP is slightly increasing about less than 1 mmHg as well as the standard deviation. In the treatment group, the table shows the intraocular pressure is decreasing gradually from the pre-treatment to the post-treatment after one week. And the standard deviation is slightly increasing after 6 hours treatment. But finally after 24 hours treatment, the intraocular pressure is significantly decreasing from 17 to 14 mmHg.

Dexamethasone

Mean ± SD (mmHg) (95% confidence intervals)

Pre-treatment

Intraocular pressure

16.4 ± 3.7

Post-treatment

Intraocular pressure

After 1stweek with maximum dose

19.7 ±3.7

p value <0.0001

Post-treatment

Intraocular pressure

Between after 1stweek and before 3rdweek with minimum dose

15.8 ±4.3

p value <0.0001

Stop treatment after 3rdweek

16.0 ±4.0

p value = 0.07

After 9thweek and intraocular pressure

14.5 ± 3.3

p value = 0.062

Table 3. The chart of mean and standard deviation of intraocular pressure between the pre-treatment and the post-treatment of the drug dexamethasone after 1st week in maximum dose, 3rd week with minimum dose and stop the treatment and measuring the IOP after 3rd week & 9th week then stop the research

From table 3, before the treatment of the dexamethasone, the mean of the intraocular pressure (IOP) is 16.4, but after the treatment with maximum dose, the intraocular pressure had significant increase from 16.4 to 19.7. And after 1st week, the treatment has change to minimum dose, then the IOP decrease about 4mmHg, to 15.8 mmHg. After the 3rd week, the intraocular pressure has slightly increased 0.2 mmHg when the treatment is stopped. In the final week (9th week), the mean of intraocular pressure is 14.5mmHg.

Esmolol

Mean ± SD (mmHg) (95% confidence intervals)

Duration of treatment

Placebo Group

Intraocular pressure before treatment

16 ±5

Mean arterial pressure (mmHg)

93 ± 11

Intraocular pressure (mmHg)

15 ±3

Table 4. The chart of mean and standard deviation of arterial pressure and intraocular pressure between the placebo group and treatment group of the drug Esmolol, all the p-value is >0.05

Table 4 shows that the esmolol working in placebo group the, intraocular pressure is slight decrease about 1 mmHg. And in the treatment group, the intraocular pressure is also decrease from 16 to 15 by 1 mmHg. But for the arterial pressure, there is difference between placebo group and the treatment group, there is 4 mmHg between them, so it is not a significant difference between placebo and treatment group in the arterial pressure

Hormone Replacement Therapy (HRT)

Range of intraocular pressure(mmHg)

Pre-treatment

16 - 20

Post-treatment

After 4thweek

12 - 15

Post-treatment

After 12thweek

13 -15

Table 5 The range of the Hormone Replacement Therapy between the Pre-treatment and Post treatment and measuring the IOP in 4th week and 12th week

Table 5 shows that before the hormone replacement therapy is about 16 - 20 mmHg in intraocular pressure. After getting treatment for 4th week, the treatment is getting decrease significantly to 4 - 5 mmHg in the range. And after week 12, the IOP has slightly increase the range from 12 -15 mmHg to 13-15 mmHg, but it is not very large difference between week 4 and week 12. And compare the week 12 result and the pre-treatment intraocular pressure. The value of the IOP shows that there is a significantly decrease after taking the treatment.

Nitric Oxide

Mean ± SD (mmHg)

Duration of treatment

Placebo Group

Intraocular pressure before treatment

14 ±1

Intraocular pressure

After treatment 5 minutes

--

Intraocular pressure

After treatment 10 minutes

15 ±1

Table 6 The mean and standard deviation of the Nitric Oxide between the Pre-treatment and Post treatment and measuring the IOP after treatment 5 minutes and 10 minutes.

Nitric Oxide

Range of papillary diameter change(mm)

Before-treatment

4.1 ±0.2

After-treatment

4.1 ±0.2

Table 7 The range of pupil diameter change before and after the treatment.

In table 6 shows that in the placebo group, the Intraocular change of before the treatment and after the treatment 10 minutes, the IOP is slightly increase about 1 mmHg. And in the treatment group, the value of IOP before the treatment is same as the placebo group. And the IOP is measured in 5 and 10 minutes after the treatment. In the 5 minutes measurement, it IOP is decreasing by 2 mmHg. And then measure the IOP after treatment 10 minutes. The intraocular pressure is increasing slightly by 1 mmHg.

In table 7, it is measuring the diameter of the pupil change, and there is no change in before and after treatment. The difference between the ranges is also the same as 0.2 mm in diameter.

Sildenafil Citrate (Viagra)

Mean ± SD (mmHg)

Dose of drug

Pre-treat

6 hours

Placebo

12.3 ± 2.2

10.6 ± 2.9

10 mg

14.5 ± 3.0

13.8 ± 3.4

50 mg

12.8 ± 3.5

9.3 ± 3.1

100 mg

12.3 ± 2.7

10.3 ± 1.8

150 mg

13.0 ± 2.4

10.5 ± 3.2

Table 8 the mean and standard deviation change of the sildenafil citrate intake 10 mg, 50mg, 100mg and 150mg. And measuring the intraocular pressure before treatment, after treatment 6 hours and 24 hours

In table 8, there is a research with 10 mg, 50 mg, 100 mg and 150 mg between 24 hours. For the placebo group, the change decrease about 1.6 mmHg after 6 hours treatment. And after 24 hours, the IOP increase to the same level as the pre-treatment. For the 10 mmHg, there is not a big change after 6 hours treatment and 24 hours treatment, the change of IOP is just about decreasing 0.7 mmHg in 6 hours and increase to 14.7 mmHg. But compare with the pre-treatment result and the 24 hours result, this is not much difference between them. For the 50 mg, from the pre-treatment to 6 hours treatment, the change is decrease to 12.8 to 9.3 by over 3 mmHg. In the 24 hours of this dose of drug, the IOP is increasing 1 mmHg after the 6 hours measurement. Compare the 24 hours and the pre-treatment, the IOP is still decreasing although the IOP is increasing after 6 hours. In 100 mg group, the IOP is change by about 2 mmHg from the pre-treatment to after 6 hours. And after 24 hours, the IOP is increasing to 13.7. And comparing with the pre-treatment and after 24 hours, the IOP is increasing by over 1 mmHg. In 150 mg group, after the treatment 6 hours, the intraocular pressure is decreasing form 13 to 10.5 and increasing back to 12.5 after 24 hours. The difference between pre-treatment and after 24 hours, the IOP is slightly decrease 0.5 mmHg. Although there is a slightly changes in the IOP after the treatment after 6 hours, but in the long term there is no significant change in the IOP

Sildenafil Citrate (Viagra)

Mean ± SD (mmHg)

Dose of drug

Day 1

Day 4

Placebo

14.0 ±1.4

14.3 ±2.1

50 mg

16.3 ±2.7

15.2 ±2.3

100 mg

13.8 ±3.5

12.7 ±1.6

Table 9. the mean and standard deviation change of the sildenafil citrate intake 50mg and 100mg

In table 9, it shows that there is not much change in the placebo group either in day 1, day 4 and day 7 measurements. And in day 7, it just have slight decreasing 0.5 mmHg, it is not very significant change. And in the 50mg treatment grourp, the IOP is gradually decreasing from 16.3 to 15.2 in Day 4 and 15.0 in Day 7. And in 100 mg group, the decreasing change is high in day 4 by 1.1 mmHg, but increase in Day 7 from 13.8 to 14.3 mmHg with about 0.5 mmHg

Triamcinolone

Duration of treatment

Range(mmHg)

Before treatment

10.2 - 18.3

1-day after

8.7 - 22.7

2-day after

10.2 - 21.2

1-week after

10.9 - 21.2

2-week after

12.2 - 20.3

6-week after

14.2 - 19.8

Table 10 The range of the triamcinolone between before treatment and after 6 weeks follow up

The biggest of the minimum and maximum intraocular pressure is after one day, the difference in this range is about 14 mmHg with minimum and maximum. The smallest range of this drug is after 6 weeks measurement, it is only have 5.6 differences between minimum and maximum.

Triamcinolone

Duration of treatment

Intraocular Pressure (Mean ± SD(mmHg))

Before treatment

14.99 ± 2.43

1-day after

15.21 ± 1.85

2-day after

14.67 ± 2.6

1-week after

15.24 ± 2.27

2-week after

15.90 ± 1.83

6-week after

16.76 ± 1.16 p-value <0.05

Table 11 the mean and standard deviation of the triamcinolone between before treatment and after 6 weeks treatment

In table 11, it shows that there is slight increase in IOP in the treatment after one day. Then the intraocular pressure decrease about 0.5 mmHg after 2 days. Then is gradually increase from the 2nd day after the treatment to 6 weeks, the range of the change is about 2 mmHg. After 6 weeks, the IOP difference between 6 weeks and before the treatment is increasing about 1.7 mmHg. It also shows that there is significant change in 6 week after.

Chapter 6 - Discussion

Acetazolamide is one of the oral medicines which is the systemic carbonic anhydrase inhibitors. The anhydrase inhibitors are controlling the fluid secreation, including corneal endothelium, ciliary process and retina due to the reaction of different carbonic anhydrase receptors, such as blockage. It is going selectively inhibit the carbonic anhydrase in red blood cell and capillary endothelium (Vital, 2003). Due to reaction of acetazolamide, it has been developed for lower the intraocular pressure for glaucoma patient in 1954 (Becker, 1954). So the acetazolamide show it have ability to decrease the intraocular pressure. Some of the studies for this drugs for the glaucoma, they will compare the effect on the flow of aqueous humor with the other topical drug, such as dorzolamide combined with timolol or acetazolmide (Toris, 2004) and Rosenberg researched the combination of oral acetazolamide and topical drug for decreasing the intraocular pressure and the formation of the aqueous humor (Rosenberg, 1998). In 1993, Chiou who do the experiment about the effect of the drugs affect on the ocular blood flow for the ocular hypertension, it shows that the acetazolamide will affect the blood flow and choroid (Chiou, 1993). So it can conclude that when the blood flow increase in this two layer of the eyes, the intraocular pressure of the eye will be decrease. Also, this drug will be use for the diuresis, and the dosage if similar to the research in finding, both are about 250mg. In the finding of this report, the result shows that there is big difference between the control group and the treatment group after 6 hours treatment. The highest one in the control group, it is increasing over 10 mmHg after 6 hours in the placebo group. After 6 hours treatment in the treatment group, the increase of range is obviously lower than the placebo group. And in the mean of the finding, it shows that there is a significant decrease in the treatment group after 24 hours treatment. So refer to our topic, it means that acetazolamide have a effect which can affect to the intraocular pressure. It is because it can be affect the creation of the aqueous humor and also got the ability to decrease the intraocular pressure.

Dexamethasone is an anti-inflammatory drugs, which will uses in hypercalcemia related with cancer (Amy). Or treat the rheumatoid arthritis and autoimmune disorder for short term treatment. Some of the studies (Pak, 2008) stated that there are many neonatologists are using this type of the drugs, dexamethasone, for the chronic lung disease case in high dose treatment. The finding shows that there is significant effect during the treatment even though the dose of the drug is in high dose or in the low dose. But in the high dose treatment, the intraocular pressure is significant increasing over 3 mmHg. So it is a big affect of the intraocular pressure. For the low dose treatment, it is slightly decrease in the intraocular pressure. So if using this drugs to do the treatment for the long term, it should be have a effective on the intraocular pressure. Some of the studies stated that the reason why the corticosteroids drugs will affect the intraocular pressure is not be clarified. But in some studies shows that there would be the reason that this drugs is affecting the trabecular meshwork which is the important system controlling the outflow of the aqueous humor (Hernandez 1983, Clark 1995). It is because the steroid cell is highly situated in the trabecular meshwork (Clark). So it will affect the gene of the trabecular meshwork and the endothelial layer of the canal of Schlemm, then will be increasing the size of the network in the trabecular meshwork which is decreasing the space of the network and increasing the intraocular pressure due to obstruct the outflow of the aqueous humor. And the other reason that why the intraocular pressure will increase is one of the enzymes call 'lysosomal' stop to react with the glycosaminoglycans (Pak, 2008) which the element can found in many cells. And it is because the glycosaminoglycans is massing up in the trabecular meshwork. And it is because of this reaction, the outflow of the aqueous humor using the trabecular meshwork is restricted (Skuta 1996, Bartlett 1999). In the finding, we would see that when the patient getting the highly dose of the treatment, the IOP will increase significantly after the treatment in 1st week. And then if the dose is decreased, the IOP will be decreasing significantly. And when the treatment is stopped, the change of the IOP is just slightly and also there is not significant change for the few weeks after the treatment is stopped.

Esmolol is a beta-adrenergic blocking agent which is used to react with the beta-1 adrenergic receptors of the heart. So it is using for lowering the blood pressure with very rapid onset and in very short time. In the finding, the value of the research between the placebo group and the treatment group, there is not significant between them, either in the arterial pressure and the intraocular pressure. But in some of the study shows that there is a significant difference in the heart rate after 1-2 minutes after the treatment, the value of the heart rate is difference between the control and the treatment group with about 8 bpm which is lower in the treatment group (Anthony, 1992). The duration of this reaction is just showing in 2 minutes after the drugs is taken. Although the high systemic blood pressure can make the IOP higher than 40 mmHg (Cunningham 1981, Donlon 1991), but Macri experiment report shows that there is not very close relationship between the general blood pressure and the intraocular pressure. In the finding and some of the result with different report, if the drugs affected the general blood pressure, it would not have a big effect to the IOP due to they are not close relationship between of them, such as the emsolol have and significant change in the heart rate at the short period of reaction time, but they do not have a significant value changing in the intraocular pressure.

Hormone Replacement Therapy (HRT), Sator experiment shows that there is significant change in the intraocular pressure with the HRT (Sator 1997). HRT is the treatment which is using in the menopause women. Some of the study shows that the replacement of the progesterone can be lowering the IOP (Alatak 1977). Some of the drugs using for the replacement for female sex hormone will be affect the base of the nitric oxide synthetase. And the nitric oxide is one of the important characters in the smooth muscle, and due to the ciliary body is one of the smooth muscle. Because of the nitric oxide synthetase affect to the smooth muscle, the IOP will have significant change after HRT due to the ciliary body has many smooth muscle which is create the aqueous humor. And one of the reason that affect the IOP, is the amount of the production of aqueous humor, so that is the why the HRT can affect the IOP.

In the finding, the nitric oxide shows that there is significant decrease with the IOP. It is using the L-argininie which is a non-toxic amino acid. It will convert to nitric oxide by nitric oxide synthase. In the research, the researcher also measured the pupil diameter which is no difference between the control group and the treatment group. So the significant of lowering the intraocular is not the change of the size of pupil. It could be suggest that due to the production of aqueous humor or the more the nitric oxide production increasing by the L-argininie intake. The report of Urabe shows that the L-argininie will cause the increase in urinary excretion of nitric oxide metabolites. Some of the report shows that L-argininie can decrease the intraocular pressure (Wiederholt 1994, Nathanson 1995, Francine 1996). The outflow system of the aqueous humor is one the site have many nitric oxide synthesis, it can be conclude that the higher the IOP is having less and less nitric oxide. And in the Nathanson finding in 1995, this states that the nitric oxide is play a important controlling function of the IOP.

For the sildenafil, there is no significant change in the IOP for use the sildenafil for long term. And in the other study, which is searching the sildenafil affect to the retinal blood vessel diameter. The result of the research is showing that there is no significant change after using the drug, sildenafil. Although the drug is used to treat the cardiac ischemic disease (Parker, 1998), and there is no change of the retinal vessel diameter and the IOP.

Triamcinolone, it is the other corticosteroids in this dissertation. This drug may help the diabetic retinopathy, macular oedema and other eye disease (Jonas, 2003). The side effect of the steroid is the increasing of intraocular pressure. So the steroid cannot be use for long term to treat for the eye disease because it will cause the elevation of intraocular pressure, it is very harmful to the optic nerve. And the higher the intraocular pressure, the higher the risk of getting the glaucoma.

In the conclusion, it can conclude that the some of the systemic medication effect can be increase the IOP, some can lower the IOP. So if the drugs can change the IOP higher, it cannot be use for a long term, such as steroid group of the drug, Dexamethasone etc. And some of the therapy can make the IOP significantly lower, such as HRT. This therapy can be develop for a new therapy for the IOP. And the other is the nitric oxide which is the harmless element to the human, it play a important roles in controlling of the IOP, so it may also be develop to a new therapy or drugs for the treatment of the glaucoma or used to lower the intraocular. Some of the drug do not make any significant different after intake with them, so they are good for long term use. Finally, drugs can be a significant change of the IOP value, so during all the eye examination, all the optometrist is requiring to ask what medication did the patient is taking and it will help to make the result and advice more accurately.

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